Multiple Sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the Central Nervous System (CNS). It starts typically between 20 and 40 years of age, and prevails over women. MS is clinically definite diagnosed after at least two neurologic events, showing demyelination in different areas of the CNS and in different times (Jacobs et al. 2000, The New England Journal of Medicine. 343(13): 898-904).
The cause of MS is still unknown, but several lines of evidence, derived from the experimental autoimmune encephalomyelitis, support the autoimmune origin of the disease (Inglese et al. 2010, NMR Biomed. 23(7): 865-872). MS is characterized by areas of demyelinated plaques or islands disseminated throughout the CNS with a predilection for optic nerves, spinal cord, periventricular white matter (WM), corpus callosum, and cortical and sub-cortical gray matter (GM). (Inglese et al. 2010, NMR Biomed. 23(7): 865-872). Lesions in MS are very heterogeneous, respect to the presence and extend of inflammation, demyelination, axonal injury, gliosis and remyelination (Inglese et al. 2010, NMR Biomed. 23(7): 865-872).
Functional Systems Scores (FSS) and Expanded Disability Status Scale (EDSS) constitute one of the oldest and most widely utilized assessment instruments in MS (Kurtzke J. F. 1983, Neurology, 33:1444-1452). Based on a standard neurological examination, the 7 functional systems are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. Each of the FSS is an ordinal clinical rating scale ranging from 0 to 5 or 6. The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
Magnetic resonance imaging (MRI) of the brain, can add certainty to the diagnosis, by identifying lesions consistent with the occurrence of demyelination.
Incorporation of IFNs to treatment of MS has opened a new pharmaceutical pathway respect to traditional immunosuppressive drug (Zaragozá et al. 2002, Farmacia Hospitalaria. 26(5): 294-301).
Interferons are cytokines with antiviral, antiproliferative, and antitumor activity, although they have different immunomodulatory characteristics. Therefore, these molecules have a great therapeutic potential in neoplastic and viral diseases. There are different types of IFNs: interferon-alpha (IFN-α), produced by leucocytes, interferon-beta (IFN-β), produced by fibroblasts and interferon-gamma (ING-γ), produced by lymphocytes-T (Zaragozá et al. 2002, Farmacia Hospitalaria. 26(5):294-301).
Particularly, several data has shown the efficiency of IFN-β in the treatment of MS. Different randomized, double-blind, placebo-controlled clinical trials has demonstrated a beneficial effect in a variety of parameters of the disease, reducing disability, frequency of relapsing, frequency of appearance of new lesions, and improving cerebral atrophy (Zaragozá et al. 2002, Farmacia Hospitalaria. 26(5): 294-301).
Despite teaching the use of IFN-β for MS, however, the art also recognizes that such treatment is only moderately effective; IFN-β at best merely slows the progression of MS, it does not cure MS. Further, the relatively high cost of IFN-β renders it financially unavailable to many patients who need it. The art thus has a long-felt need for a more effective treatment for MS.